Zhuo Haiyan, Fan Jinhai, Zhang Bifeng, Shi Yixian, Zheng Liqing, Chai Yihong, Yao Lvfeng
Department of Hepatology, Mengchao Hepatobiliary Hospital of Fujian Medical University, No. 312 Xihong Road, Fuzhou, Fujian, 350025, P. R. China.
Department of Hepatology, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, Fujian, 350025, P. R. China.
Open Med (Wars). 2022 Sep 6;17(1):1455-1465. doi: 10.1515/med-2022-0549. eCollection 2022.
Genetic variation in UDP-glucuronosyltransferase 1A1 gene (UGT1A1) is a lithogenic risk factor for gallstone formation. This study aimed to assess genotype and allele frequencies of common UGT1A1 variants in patients with gallstone and hepatitis B virus (HBV)-related hepatic failure. This study enrolled 113 healthy individuals (CTRL), 54 patients with HBV infection (HBV), 134 patients with gallstone-free hepatic failure and HBV infection, and 34 patients with gallstone-related hepatic failure and HBV infection (GRHF). Peripheral venous blood samples were collected for genomic DNA isolation. Polymerase chain reaction amplification was carried out for UGT1A1, followed by direct sequencing. Analysis for genotype and allele frequencies of UGT1A1 variants (, , , and ) was performed. The allele distributions of the four groups did not deviate from Hardy-Weinberg equilibrium. Allele (A) and genotype (CA) frequency distributions of were significantly different between GRHF and CTRL, or between GRHF and HBV. GRHF and CTRL exhibited significant differences in allele (A) and genotype (CA) frequency distributions of UGT1A128. Linkage disequilibrium analysis suggested that haplotype G-G-[TA]7-T may be associated with gallstone in HBV-related hepatic failure. Our data reveal that UGT1A127 and UGT1A1*28 variants are significantly observed in patients with GRHF compared to healthy individuals.
尿苷二磷酸葡萄糖醛酸基转移酶1A1基因（UGT1A1）的遗传变异是胆结石形成的致石危险因素。本研究旨在评估胆结石患者和乙型肝炎病毒（HBV）相关肝衰竭患者中常见UGT1A1变异体的基因型和等位基因频率。本研究纳入了113名健康个体（对照组）、54名HBV感染患者（HBV组）、134名无胆结石的肝衰竭且HBV感染患者以及34名与胆结石相关的肝衰竭且HBV感染患者（GRHF组）。采集外周静脉血样本用于分离基因组DNA。对UGT1A1进行聚合酶链反应扩增，随后进行直接测序。对UGT1A1变异体（27、28、36和47）的基因型和等位基因频率进行分析。四组的等位基因分布均未偏离哈迪-温伯格平衡。GRHF组与对照组之间，或GRHF组与HBV组之间，27等位基因（A）和基因型（CA）频率分布存在显著差异。GRHF组和对照组在UGT1A128等位基因（A）和基因型（CA）频率分布上表现出显著差异。连锁不平衡分析表明，单倍型G-G-[TA]7-T可能与HBV相关肝衰竭中的胆结石有关。我们的数据显示，与健康个体相比，GRHF组患者中UGT1A127和UGT1A128变异体的观察频率显著更高。
